Doc 0000151908

The image displays a stylized graphic of a vault door on the left, with bright blue light emanating from it. To the right of the vault, bold white text reads "THE BLACK VAULT." Below this, white text on a black background explains that the document was obtained from "The Black Vault," an online database of declassified government documents, specifically mentioning the MKULTRA/Mind Control Collection and providing a URL. There are no photographs, handwritten annotations, signatures, stamps, forms, diagrams, tables, or redactions visible on this page. The visual content primarily serves to frame the textual information about the source of the document. ./ ~ \ df)/S · TlTLS OF PROJ£C'l"l Addlct!on L1ah111t.1ea ot Synt.hat!c fer Codeine. Subst1tu~cs ObJ~ct1VttS% To t!:ld. a S!<"l.4th~t.1c: a~l~.:sic and nnt1 tt:.sslve c1ng which wu14 be as sate trcm t-.'1~ po1nt ot v!ev or t.o~iclty and add1ct1~~ 1lab111ty as 1s eodelne. ABSTRACT (OR Stli,l·IA."!\Y) OF RESlJL.TS or a. S!nee start projectt ·' ·or This port1ol1 t.ha summary ot results .covers the was pcr1od.trc~ .1 July 1151 to )0 October 19$7. The proJact undertaken no drug available Which as b~eaus~ syn~h~tlc •~s ~~s sara rezpect to toxicity and 11ab111ty as wiL~ ad~lctlcn ~~s code!ne. Stnca 7$ per cent ot the e¢untryts for narcotic ne~ds drugs are ror than fer potent or tho codein~, r~ther ~~la~slcs morph!ne United must continue to stockptfe t~a, th~ Stat~s tor are op1~~ ~~t11 ad~~~t~ aynth~t!c s~stltut~s codeln~ developed. Tho! rola of t..~e 111!-t-i Addiction Res~arch Cent.~r !n thls ldlleh was at the or the 1nv~st1~ation, b~oun re~~e$t Cor::m!tt.~~ on Drug Addict.!on a:l:i t!circot!cs o! tlls r!ational Research Co~~eil~ constets of. the dat~rm!~tlon of ndd!ctlv3 properties or.t.h~.naw drugs. 7h.o cllnlcal ~valuat!o;l or tha ... ., . ... .. During~~ tee·~ ltt.:'~. period ot l JulJ 1951 to .31 · 46 n.:v drugs or mixtures o.t c1rUgs have bean t.cst.~4 tor addict.1ve l Detailed eoncerntng l potcnl1a11t1e~. 1nfcr~~t1o~ thes~ su~~tan~zs j ! can be round.· in the annual for 1954- 1956. Two r~o:-t:s t.brou~'l subslancas were out$tandlng as pos:1bls substitutes ~hlch to~ codeine tor cou,h These were1 au~,rcsslcn o~ ~re to~~d. (1) (dextromethorphan), and (2) a-3-~ethoxy-~~cethylr,~rph!nan narcotine. reports to 1nd!cate that Fur~~=r ellnJ~al eont1nu~ is etiUivalent. t.o c:.od41ne ln potency. 4cZxtro~l:Jt.horphan a!ltltu~siV\a lt.• there1"ore a very aat.1s!actory codelna subst1tut.a ror 6 se~ rell~.r o:r cou9h. It 1$ :il7:eady, avn.tlabla and en sale 1n the · United states. P..arcotlne ls now on ~le and report.~ of: clJ.nlea1 t.rtn1~ or th13 oruo are Indicating that. it may also be a useful for ant1tus~!vz ~u~~tituta coc~ln~. , a co;::po1.:n<l w!'tic.h would baas er.rcct1ve e.ndQ3 saro as codsin~ 1u C;;ntlnuL~g cll~l.!cal cr substltutes !or codeine in rlf!11ef pein. C.o::lpl'lta data on· toxicity cl!n!cal ccnd1tions hovzvcr, not und~r a~e, y~t avallahl~. This ·drug is no•J ba1no ln t.hra l!n.lt.cd States by Eli !..1lly oarJ-..et~d A-Y97 .... •. -· .o.J?g b. lha current ,....,crttn\i per1odt • During the current reporting period tha add1ct1v• potent1alit._1~s ct tive tru~s t1crra evaluated. -wholly or In part. _Tha results are presant.E:d be lot#:-t\l\d.::r .lncUv1dua1 headings: ;ewtor..oxybutane This document is a declassified page from a research project, likely related to drug development or testing. The majority of the page consists of typed text detailing the project's title, objectives, and an abstract of results. There are no photographs, diagrams, or tables present. Two handwritten annotations are visible at the top right: "#115" and "#6". Further down on the right side, there is another handwritten annotation: "A-400". The document shows no official stamps or any visual evidence of experimental procedures or facilities. This ·drug is no•J ba1no ln t.hra l!n.lt.cd States by Eli !..1lly oarJ-..et~d A-Y97 .... •. -· .o.J?g b. lha current ,....,crttn\i per1odt • During the current reporting period tha add1ct1v• potent1alit._1~s ct tive tru~s t1crra evaluated. -wholly or In part. _Tha results are presant.E:d be lot#:-t\l\d.::r .lncUv1dua1 headings: ;ewtor..oxybutane ( c-t!ropo:(l:?,:':;<!,ne). \iork on this compound w-as l- . and. the results ruported to tha Drug Addiction co~let~d Com=ltt.~e ln January 1956. The results contlnue.to support those previously described. In tormcr- addlct.s th$ drug does . A .. • .. \ . o .. l t . 1- · - ~ -' - ·· C<! ¥ !> W 112 . 4 4. " . " . 11 . . . . . . . ~ . . . . . . . ., . ~ ~ . w . r- ;, - ._~• - .6 v "" 4 ,. . ~ . . .. , .. ~ .. , .. . t . rr · ~ ~ ' " - ' 1- V "~ - . - c- - f • r ' ; -w - t . t . i , l - ~ • · w .. sc! . " .. · _ ' ··l 4 ' U ... ; . .. J ,. lt do~$ suppre~s abstin~e rr~ .- or tercd to no11tol.::rcnt. some c~ronlcally voluntc~rs d~gre\1 to the tol~rancs ~adat!v~ e!!~cts 1~ ob~erved.- Follo~tng 1tab1lity t:1:lchl h~H.;:V:!r,_ \.."".l!l far lcs::l than that. 0£ CO<hdne. Tha Addietion has that D~g Ccn~ittac th~r~tor~ recomm~d~4 b-e .bv the u. s. r.arcct.!c: ·controll~d "" - . .. # . (2) Norr.orphtne. St.uulcs ot this agent wcr~ unc~r­ or t.aken tor tvo reasonsJ !lrst, it __ the prcct:rsor 1:~ t2".~ ;"".Or;l!llnc· antagonists wh!c:h acd1ct!on 1 b!J111 ty t!lan l~ve l~3S or does =orph!neJ 1t is a metabo11e product ~~condly, n~r~l mcr-~h!nii: l-111ieh. 1s formed by U-d~i:t.hylat!.on ot morphine. · l\s tolerance to morphine is acqu!r<!d.in r.:ale rat:l the ab111ty ot or the to ls redueed. Studies its 11Y~r 4~ethy1ate ~orph!ne acld1ct1on llab!l!ty, theretor~,_seem to be J..r:portant t.h.co:-et1..: cally z.s vcll aa praet.!cally. In s-ingle doses, norr.:orphin:: Is less potent than in 1nduclns scdat1cn. In t~r r~rphi~c r~?catad l't..ovever. lt 1s potent ::wrphlne. On chronic t!ose~ ~re t~..rut or the dose as a~1n1strat1on, nc~rphlne ear~ot h~ ra!~ed or rapidly or to a:; high a 1 evel a.s can the dose marphln~. Tolerance The page is filled with typed text on white paper, with a few darker smudges and small flecks, possibly from an older, dot-matrix printer, and some minor ink spots that do not obscure text. There are no photographs, official stamps, forms, diagrams, tables, or redactions visible. In the bottom right corner of the page, there is a handwritten annotation "A-399" in black ink. praet.!cally. In s-ingle doses, norr.:orphin:: Is less potent than in 1nduclns scdat1cn. In t~r r~rphi~c r~?catad l't..ovever. lt 1s potent ::wrphlne. On chronic t!ose~ ~re t~..rut or the dose as a~1n1strat1on, nc~rphlne ear~ot h~ ra!~ed or rapidly or to a:; high a 1 evel a.s can the dose marphln~. Tolerance to sedative e!!ncts slowly than ~~e develo~s ~~re or -tratlon n-allyl.nor=.orphine to chronically lnt.c.:dc::ted p~l·sons v!th. r,.orSiorphlnc precipitates m!ld s~t.c;:w ot abstinence. ~'!lQn nerl!'.Qrph1nc 1:s wlthdra\ln a of arte~ p~riod ~~ron1c lnto.xlcatlo~ A-5CJ7 .... * -- addlctlvc 11ab111t.y w"!lich is lc&as than that or cod!!ine• . ~retbably The chnra.ct~r lstlcs ot norn::wphln~ arc such· that, J.t it 1:s an- anal!Jcste !;A r;~n, it. should be c.n excallu.'lt drug';in condi tlon~ 1-rlt.h c:hron.1c ;Jain. as~1ated (3) Stud!as ot norcodcine vere ~oreod~!ne. ~,der- taken because ot low addietiveness or the parent cerr.pound, L~e normorphine. These studie3 are still 1neo:plete. Prelimir•ry studies indJcat.e that.. noreode!ne will probably_have t...'la sam.:~ relat1onsh1p t.a as ha:s to morphine. In cot!~!na n~r.nlerph!na repeated dose, n::>rco.d·;?-.ln3 is ln !ncuclng rcor~ pot~nt. szd~t1on extr~~clynlld following wlthdra~~l of norcod~1~a after chronic lntox!catlon. drua is or;:;.lly, so it is a ;.ronlsl:tg Th·~ ef!act!v~ sul>stlt.ut.e !or eocelna; untortunatcly, h~wavcr, it is nat a synthetic. (4) L-1-l~~.!0}:}7:':.orph !!"':an (Nor! evornhnn) • 1h1s or eompou.:\d 1: the non:-.or?hine in the morph1nnn ser!es. an.alogu~ Cn1y ;>rcl in!nary in!\:::rmrlt. !on is as yet. availabl Singl c dosa:s - ~. . . - :-· ·-:_-~_·.··. ~- .-•. ·.'. . . - :- ~ . -- ~- ._.. :: - _ r_ f_. _ ·= - ---.-., -..... - ·:: .~.,--J •#-.... - .,-)~. ....... _~ _ . •~ _ .,.... . • ""•, ~--._ _·- ......,... # : - • . • .. -~. . , · . • : " ! . -..~. :. - .J~. ,w., . ....... ._..., ~..... .."."_':."..'. _f'. .;. c~t cr~a tcr dcsc.r t.luln the eddlct 1n~ d~~e ot J::orphln:.!. ;\t the -- (5) t-J-r.le~'loxy-N-p:v.:nethxt~~rrhim.tn 0HH-72<36Al· _ We previously raported that this Con;>oWld partially suppr~s:.ed. . cbstinanc~ tr~m r::orphinc. This rc3ult. wa.s entlrtly unex;H:ctcd ·· · since a CQngoancr, d-3-hydroxy-N-phe.ncthylmorphlna, \.-'aS !naet1ve -- ln thls th.t$ result. could possibly hav<: rcsp~ct. Sine~ bc~n due t.o cont.al:11ru~t1on with the potent 1-rorm ot t.he drug, purtfied o: th!a obtained esp~c!ally ~le3 co~ound ~ra ~~d t.s::st.ed. The pur1!1cd drug cl$o fart!y Gt.';)p~es~ed e.l>st.tncnc-a .m.oriJhlnc. This cor..tir:r-.3 tl1~ previous rcsul t. and c;<cluds:s tha or The document is a typed page with a handwritten annotation at the bottom right corner that reads "A-398". There are no photographs, stamps, forms, diagrams, tables, or visual evidence of experimental procedures present on this page. The content consists solely of text detailing research on a drug called d-propoxyphene and its addictive properties. !naet1ve -- ln thls th.t$ result. could possibly hav<: rcsp~ct. Sine~ bc~n due t.o cont.al:11ru~t1on with the potent 1-rorm ot t.he drug, purtfied o: th!a obtained esp~c!ally ~le3 co~ound ~ra ~~d t.s::st.ed. The pur1!1cd drug cl$o fart!y Gt.';)p~es~ed e.l>st.tncnc-a .m.oriJhlnc. This cor..tir:r-.3 tl1~ previous rcsul t. and c;<cluds:s tha or levo-Isomcr. The nddlction drug ls to 11~bl11ty th~ jud9~d -. - ·~: rat.udles on the poss!~l~ 1·)-m::thox~,.rr!lr?hinan, cod~in~ a.~l~g·..1e ot norclro~oran, "'i 11 lie J.nl t!att!d and co4:'!i'a~ed 11:! th tha rest1l ts A-J.9r • . ....... ..... -.· / Long Ranaea r:c intend to con·t.!nuo t.'l\1 a.!urch tor for unt!l drCGS arc, in Su~stltut~S COd~1ne ~ra !O~~d ~lch the o;>1n1on of t,h(: C:l::2:1ltt.a~ on ~.-ug Addiction and !:arcotics ot the NationAl Research Council, sattsfactor7 ~a~l~tely tor aubst1tut~a codctn~. ! JtEPOnTs Alrn PUBL1C\T!0~5 (c-.lrl:tg eurr~nt t"·Jport period). 1. Fra:cr, H. r •• Isbell, H.; Furth2r on nn~ stu~i~s - d·l1.2-Dlphcnyl-!.;.;.D!z:~t!tyla..""l1no-J-He.thyl-Z-Propicnoxy!Jutc::e ( d-Propox~?hcnll) • Addendum Hln. lot.h Ha~tms. Cor.;n. on Crug Addiction and Narcotlc:. National Connell. lndlanapolis, Res~~~ Ind. 21-23 Je:nuary 19.$7. 2; Fras..:r, H. P., and lsbc-ll.t M.t Addiction Liabll!ty ot 1. 1-(2"morp~ol!nathyl)-4·phenyl-~-carbcthoxy­ plpcridlnc (~IH-7::]). (NlH-7292). plpcridln~ 111. l-.3-Hot.hoxy...N-ph_anct.hyloorphlP~n (NlH-7.)62} • C!nH ... pyrrol1dln~ 7L~22). 21-23 Janu:!ry 1957• • ... .{ ~ ·) ' 3• ·Fraser, H. F., l~bell1 H., L'ld Van !!orn, a. D.: j i or l z.rtccts o! Horphlnc az Co;:;;arcd. wl~h ,%1 E.txt.l!I'\1 i:orph1nc plua l .. i~ . Ola..'llnc-?h.enyl-T:l1atole (Da~tatola). ·. Anc~t.hA!s!c1ogy, - 1~: 5.31· l ·';· .·. . : , M.n. Harris !ebcll, D.tt't;!CtOl" .: ::r:: , -. ,· .,. . .. .. The document is a typed page of text with a few handwritten annotations. At the top, there are three circular shapes, two filled in black and one empty, which might be part of a bulleted list indicator. In the top right, there are a few instances of ink-like specks scattered across the page. In the bottom right corner, there is a handwritten annotation "A-397". A shaded area is visible at the bottom of the page, which appears to be a partial image of the page itself or a stamp. The text discusses "Normorphine" and its effects, potentially related to drug studies or experiments. This page is a scanned document containing typed text and handwritten annotations. The text discusses the addictive liability of various drugs, including norcodeine and L-3-Hydroxymorphinan. There is a handwritten annotation in the lower right corner which appears to be "A-396". The document appears to be a declassified government report, as indicated by the typeface and the absence of any classification markings, which are common on such documents. There are no photographs, diagrams, or forms present on this page. The page is generally clear, with no significant redactions or obscured content. The page contains typed text that appears to be a scientific report or memorandum, with some handwritten annotations. On the right side of the page, the handwritten annotation "A-395" is clearly visible. There are no photographs, official stamps, forms, diagrams, tables, or visual evidence of experimental procedures present. The text discusses a compound and its effects related to drug abstinence and addiction liability. This document appears to be a page from a typescript report with handwritten annotations. The text details a search for codeine substitutes and lists reports and publications related to drug addiction and narcotics. There are multiple enumerated lists and sub-lists presenting chemical compounds with associated NIH numbers. The only visible handwritten annotation is "A-394" in the lower right corner of the page. The document contains no photographs, stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures. This page contains a typed bibliographic reference for a scientific article and an associated handwritten note. The reference entry, numbered "3.", lists authors Frasier, Isbell, and Van Horn, and details an article on the effects of morphine compared to a mixture including daptazole, published in Anesthesiology in 1957. Below this, a handwritten note reads "Harris Isbell, M.D. Director". In the bottom right corner, there is a handwritten annotation "A-393". The page also shows a handwritten word "Hlatkh" on the left side. There are no photographs, diagrams, official stamps, or redacted content visible.